suicide risk, especially among psychiatric patients44. This is in line with the known effect of altered thyroid function on mental health43. In a recent genome-wide analysis, we observed that hypothyroidism is genetically correlated with several behavioral traits including fatigue, anxiety, depression, loneliness, and mood swings45. Based on these findings, we hypothesize that the region identified may affect suicide risk via its role in regulating thyroid function. Additionally, the three substances (cocaine, nicotine, and opioids) that showed an interactive effect with rs8052287 on SI have been investigated previously with respect to thyroid homeostasis. Cigarette smoking appears to affect thyroid function with a dose-related effect linking cotinine levels to thyroid function and thyroid autoimmunity46. Cocaine abuse has been linked to the disruptions in the hypothalamic-pituitary-thyroid axis47 and cocaine use has been suggested as a possible trigger for thyroid storm48. There is a growing literature on the effect of opioids on the endocrine system and opioid-induced endocrinopathies49. Acute administration of various opioids has been shown to alter thyroid-stimulating hormone and thyrotropin-releasing hormone consistenly49. However, conflicting results were obtained by studies investigating thyroid function in long-term opioid users and controls49. Although the exact pathway by which the combination of CoD, ND, and OD interacts
